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The historical artefacts of parchment are prone to degradation if the storage conditions are improper due to the collagen structure having a limited stability under physical, chemical, and biological agent attacks. The parchment structure is difficult to characterize due to the variety of manufacturing traditions (eastern/western), intrinsic variability of skins (i.e., species, breeding variation, living conditions, effects of pathologies, etc.), biodeterioration, and aging, and the main concern in its analysis is its uniformity. The deterioration of parchment collagen produces a rather stiff or in some circumstances, a relaxed structure. Any intervention or treatment of unique, very precious cultural heritage artefacts must not negatively influence the properties of the component materials. Gamma irradiation is a relatively new technique of bioremediation. Data on the leather properties pre- and post-ionizing radiation bioremediation treatments are few in the literature. Fewer data are available on the historical leather and parchment physical chemical characteristics after ionizing gamma irradiation. This research had two main objectives: (i) the characterization of the parchment structure's uniformity across the analyzed areas and its mechanical properties, i.e., tensile stress by mechanical tests and ATR-FTIR spectroscopy; and (ii) to establish parchment tolerance when exposed to ionizing gamma radiation as a pre-requisite for cultural heritage preservation irradiation treatment. It was found that the mechanical tests and ATR-FTIR spectroscopy may identify changes in the parchment's irradiated structure and that the preservation of cultural heritage parchment artefacts may be performed at maximum 15 kGy gamma irradiation dose.